Abstract
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Introduction: Previously presented flortaucipir (FTP) image interpretation methodology demonstrated diagnostic power for predicting autopsy-confirmed neurofibrillary tangle (NFT) scores of B3 (Braak V/VI)1. Quantitation using an early tau volume of interest (ET)SUVr 2 improved sensitivity to intermediate (B2) Braak pathology3. In this work, we present groupwise surface maps for visualization of FTP retention based on NFT scores and compare with the proposed Braak staging pattern4,5.
Methods: We included 60 subjects from a phase III autopsy study (Table 1) that underwent ante-mortem flortaucipir PET imaging. Neuropathological findings were recorded according to NIA-AA recommendations by two experts. Flortaucipir PET images were processed and spatially normalized to the MNI template according to procedures described previously6. SUVr values were calculated for each FTP image relative to a white matter reference region7. Subjects were grouped based on NFT score for groupwise mean and standard deviation SUVr image creation. These images were projected on the FreeSurfer FsAverage template8. Vertex-wise z-scores were estimated relative to a database of sixteen young controls from a different study6. Groupwise mean and z-score surface maps were created to represent groupwise flortaucipir retention.
Results: The surface maps of mean SUVr and z-score values of subjects with a B1 (N=7) NFT score (Braak I/II) revealed slight elevation in flortaucipir signal in isolated vertices of the medial/lateral temporal lobe (Figure 1A and 1D). For B2 (N=15) NFT score subjects (Braak III/IV), we observed elevated flortaucipir signal in the inferior temporal, fusiform, middle temporal gyri and inferior parietal lobe (Figure 1B and 1E). In B3 (N=38) NFT score (Braak V/VI) group, we observed elevated flortaucipir signal in temporal, parietal, precuneus, and frontal regions (Figure 1C and 1F). These findings broadly align with the proposed Braak staging patterns.
Conclusions: In this first of its kind study, we present visualization of ante-mortem FTP retention. While the sample size is limited, the FTP retention patterns in the surface maps at a group level are in agreement with the neurofibrillary tangle staging scheme proposed by Braak. References: 1. Mintun, M. A. et al. Relationships between flortaucipir PET signal and tau neurofibrillary tangle pathology at autopsy. in Human Amyloid Imaging 304 (2019).2. Kotari, V. et al. Early tau detection and implications for disease progression. in Alzheimer’s & Dementia vols O5-01-06 (2019).3. Southekal, S. et al. Temporal Lobe Flortaucipir Quantitation may improve the detection of Intermediate Neurofibrillary Tangle Pathology in an Autopsy-Validated Cohort. in Alzheimer’s & Dementia (2019).4. Braak, H. & Braak, E. Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol. Aging 16, 271-278; discussion 278-284 (1995).5. Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H. & Del Tredici, K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. (Berl.) 112, 389-404 (2006).6. Pontecorvo, M. J. et al. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain140, 748-763 (2017).7. Southekal, S. et al. Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal Intensity. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 59, 944-951 (2018).8. Dale, A. M., Fischl, B. & Sereno, M. I. Cortical surface-based analysis. I. Segmentation and surface reconstruction. NeuroImage 9, 179-194 (1999).
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